(3AS,4S,6AR)-4-METHOXYTETRAHYDROFURO[3,4- B]FURAN-2(3H)-ONE

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-10-12 to 2005-11-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

443-930-6

EC Name:

-

Cas Number:

866594-60-7

Molecular formula:

C7H10O4

IUPAC Name:

(3AS,4S,6AR)-4-METHOXYTETRAHYDROFURO[3,4- B]FURAN-2(3H)-ONE

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Name of test material (as cited in study report): TIC2782 (T002907)
- Substance type: White solid
- Physical state: solid
- Analytical purity: 99.9 %
- Purity test date: No data
- Lot/batch No.: 00467090 (= charge 05C0836)
- Expiration date of the lot/batch: 2006-05-04
- stability of test item dilution: unknown in PEG300
- Stability of test item: stable under storage conditions
- Storage condition of test material: At room temperature (range of 20 +/- 5 °C), light protected.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HanRcc:WIST (SPF) from RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf / Switzerland
- Age when treated: Males: 8 - 9 weeks; Females: 12 -13 weeks.
- Weight at first day of treatment: Males: 236.9 - 246.4; Females: 188.3 - 205.4g.
- Fasting period before study: unknown
- Housing: Standard laboratory conditions; during acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation.
- Diet: Ad libitum, pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet.
- Water: Ad libitum, community tap water from Füllinsdorf
- Acclimation period: at least 6 days, under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30- 70 (values above 70% during cleaning process possible)
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 / 12
- Other: Music during the daytime light period.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Remarks:

PEG300

Details on dermal exposure:

TEST SITE
- Area of exposure: backs of the animals
- % coverage: 10% of the total body surface
- Type of wrap if used: gauze patch which was applied to the intact skin with a syring and sovered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm tapwater and dried with disposable paper towels.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL/kg
- Concentration (if solution): 0.5g/mL
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE (PEG300)
- Amount(s) applied (volume or weight with unit): 4 mL/kg
- Lot/batch no.: 1157790 51105271
- Purity: no data
- justification: the vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 males, 5 females all 2000 mg/kg body weight (total 10 animals)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Moratilty / Viability: daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 ours after adminstration on test day 1 (with the clinical signs) and twice daily during days 2-15. clinical signs: daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 ours after adminstration on test day 1 and once daily during days 2-15. Body weights: on test days 1 (prior to administration), 8 and 15; other: local signs: Once dailing during days 2-15.
- Necropsy of survivors performed: yes. All animals were killed at the end of the observation period by Carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.

Statistics:

No statistical analysis were used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured during the study.

Clinical signs:

No systemic or local signs of toxicity were observed during the study period.

Body weight:

The body weight of the animals was within the range commonly recorded for this strain and age.

Gross pathology:

No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of TIC2782 (T002907) after single dermal administration to rats of both sexes, observed over a period of 14 days is: LD50 (rat): greater than 2000 mg/kg body weight. Therefore T002907 is not classified based on CLP regulation.